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This phase II trial studies how well ipilimumab works in treating patients with human papilloma virus (HPV)-related cervical cancer that has come back or that has spread to other areas of the body. Monoclonal antibodies, such as ipilimumab, can find tumor cells and help kill them or carry tumor-killing substances to them.

Immune-Related Complete Response (irCR): complete disappearance of all lesions for at least 4 weeks from the date of documentation of complete response. Immune-Related Partial Response (irPR): The sum of the products of the two largest perpendicular diameters of all index lesions is measured and captured as the SPD baseline. At each subsequent tumor assessment, the sum of the products of the two largest perpendicular diameters of all index lesions and of new measurable lesions are added together to provide the Immune Response Sum of Product Diameters (irSPD). A decrease, relative to baseline of the irSPD compared to the previous SPD baseline, of 50% or greater is considered an immune Partial Response (irPR). irStable Disease (irSD): does not meet criteria for irCR or irPR, in the absence of progressive disease.

Biologic Responses of Exposure to Ipilimumab by Analysis of Lymphocyte Subsets and Assessment of Cervical Cancer-antigen Specific T Cells Anti-tumor Response [ Time Frame: Up to 1 year ]

Disease Stabilization [ Time Frame: Up to 1 year ]

As per RECIST v1.1, stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Progression Free Survival [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year ]

Progressive disease (PD), as per RECIST v1.1, is defined as at least a 20% increase in the sum of the diameters of target lesions and an absolute increase of at least 5mm, or the appearance of one or more new lesions. Computed using the Kaplan-Meier method.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed metastatic or recurrent cervical cancer of squamous, adenocarcinoma or mixed histology type not suited to definitive localized therapy; HPV status will be confirmed for all patients following enrollment

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as > 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

Previous therapy:

Patients may have undergone surgery and/or received definitive radiation or chemo-radiation for localized disease in the past

Radiation treatment with curative intent (radical chemoradiotherapy or adjuvant chemoradiotherapy) must have been completed >= 3 months prior to enrollment

Note: patients who completed palliative radiation therapy 2 weeks before start of ipilimumab are allowed as long as this does not affect measurable disease

Patients must have been exposed to platinum chemotherapy either as part of definitive chemo-radiation OR as first line systemic treatment for metastatic disease

Patients MAY have received up to two prior lines of systemic chemotherapy for metastatic or recurrent disease; patients with metastatic disease at first presentation MUST have received one platinum based line of chemotherapy

All chemotherapy must have been completed >= 4 weeks prior to enrollment with radiologic evidence of radiological disease progression

Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Life expectancy of greater than 3 months

Leukocytes >= 3.0 x 10^9/L

Absolute neutrophil count >= 1.5 x 10^9/L

Platelets >= 100 x 10^9/L

Total bilirubin within normal institutional limits (except in Gilbert's syndrome)

All radiology studies must be performed =< 3 weeks prior to the start of therapy

Subjects with treated and asymptomatic brain metastases are eligible; patients that received palliative radiation (for brain metastases) are eligible if they have been asymptomatic for at least 2 weeks with use of maintenance steroid therapy, and last received radiation at least 4 weeks prior to start of therapy

Ability to understand and willing to sign a written informed consent document

Ongoing prior toxicities related to previous treatments must be recovered to =< grade 1 at the time of registration (with the exception of alopecia or skin depigmentation)

Patients are willing to undergo tumor biopsy pre-treatment (within 14 days prior to registration) and post-treatment (within the first week of cycle 2 onset); patients who consent but have tumor that is not amenable to safe biopsy will be allowed to enter the trial/continue therapy as per protocol if this has been addressed and permission is granted from the lead consortium principal investigator (PI) prior to registration continuation of treatment

Exclusion Criteria:

Patients who have had chemotherapy < 4 weeks prior to enrollment (< 6 weeks for nitrosoureas or mitomycin C) or who had radiation therapy with curative intent < 3 months prior to enrollment (< 2 weeks for palliative radiation therapy) or those who have not recovered (=< grade 1) from adverse events related to previous treatments are excluded

Patients with a history of prior treatment with ipilimumab or other cytotoxic T-lymphocyte antigen 4 (CTLA4) agonists or antagonists, anti-programmed death 1 (PD 1) antibody, cluster of differentiation (CD)137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded

Patients who are receiving any other investigational agents

Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and Myasthenia Gravis, multiple sclerosis)

Patients with known immune impairment who may be unable to respond to anti-CTLA 4 antibody

Any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab

Patients requiring systemic steroids are excluded; narcotics should be used with caution

Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ipilimumab

Patients with active or chronic infection with human immunodeficiency virus (HIV) who have raised viral loads or uncontrolled disease are ineligible; those patients however who exhibit minimal viral loads with good control whilst on stable anti-viral regimen may be considered if they meet all other eligibility criteria